The major area of study of this laboratory is the role of the epidermis as an immunologica1 organ. We have found that epidermal Langerhans cells are derived from precursor cells in the bone marrow and play an essential role in many of the immunological reactions affecting the skin. We have also identified an epidermal Interleukin 1-like cytokine which may serve as a second signal in the generation of T cell responses as well as a proinflammatory agent affecting other cells - especially neutrophils. We have demonstrated that when epidermal Langerhans cells are cultured for 2-3 days they become very potent antigen presenting cells compared to freshly prepared Langerhans cells. We have therefore utilized cultured Langerhans cells for the generation of primary immune responses in resting unsensitized T cells. We have demonstrated that when cultured cells are modified with hapten, they can generate primary immune responses. The sensitized T cells thus generated respond preferentially to the same hapten in vitro. We have also concentrated our efforts on the characterization of murine dendritic thy 1 positive epidermal cells. We have utilized highly enriched populations of freshly prepared cells and identified their T cell nature by demonstrating that they express gamma delta-like T cell receptor along with the associated T3 components. As these cells are also present in nude mice they may represent an extra thymic source of T cells in nude as well as normal mice. The other major focus of this laboratory has been the study of the function of class II MHC bearing keratinocytes which appear in humans and mice during cell-mediated reactions in the skin. We have demonstrated that these cells can 1) present peptide fragments to T cell hybridomas, 2) serve as targets for class II specific cytotoxic T lymphocytes, and 3) induce secondary alloreactive T cell responses, although the first and third are performed only poorly. Our recent studies demonstrate that these class II bearing keratinocytes induce specific immunological unresponsiveness.